Repeated KI Prophylaxis in Case of Prolonged Exposure to Iodine Radioisotopes: Pharmacokinetic Studies in Adult Rats
To propose a new and effective dose regimen for stable potassium iodide (KI) repeated prophylaxis in case of prolonged exposure to radioactive iodine.
The pharmacokinetics of iodine was determined in rats by compartmental analyses after intravenous and oral administrations of the optimal dose of 1 mg/kg KI, which was previously selected in a dose-effect study. The thyroid protection against iodine-125 incorporation was followed during 24 h after a single oral dosing of KI. A repeated KI prophylaxis was modeled using initial estimates of iodine pharmacokinetic parameters.
A dose regimen consisting in administrations of 1 mg/kg daily for 8 days was selected and studied. Plasma iodine concentrations predicted by simulation were verified by experimental data and varied after the third dose of KI between 174 and 1190 μg/l. The inhibition study of iodine-125 binding in the thyroid as a function of the time showed that the protection effect of KI could be correlated to stable iodine plasma concentrations. Hence, a theoretical decrease in iodine-125 thyroid uptake from 63 to 88% could be achieved in a 24 h-interval between two KI doses.
Given the satisfactory levels of thyroid protection, this dose regimen could be envisaged in order to extent KI indications for repeated prophylaxis.
Key wordsdose regimen potassium iodide prophylaxis pharmacokinetics pharmacokinetic-pharmacodynamic relationship rats
Acknowledgments and Disclosures
The authors are thankful to the Central Army Pharmacy for providing solutions of KI, Dr. Delphine Denais-Lalieve (DVM), Mélanie Berchet, Amandine Sache, Romain Granger and Frédéric Voyer from the animal experiment support group of IRSN for animal care. These studies were supported by the research program in Nuclear Safety and Radiation Protection of the French National Research Agency (ANR) (contract number ANR-11-RSNR-0019). The authors declared no potential conflicts of interest with respect to research, authorship and publication of this article.
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